Vol. 334 No.
13 CURRENT CONCEPTS
REVIEW ARTICLES
CURRENT CONCEPTS
ASSESSMENT OF QUALITY-OF-LIFE
OUTCOMES
MARCIA A. TESTA, M.P.H., PH.D.,
AND D ONALD C. S IMONSON, M.D.
S INCE 1948, when the World Health Organization
defined health as being not only the absence of dis-
ease and infirmity but also the presence of physical, men-
tal, and social well-being,1 quality-of-life issues have
become steadily more important in health care practice
and research. There has been a nearly exponential in-
crease in the use of quality-of-life evaluation as a tech-
nique of clinical research since 1973, when only 5 arti-
cles listed “quality of life” as a reference key word in
the Medline data base; during the subsequent five-year
periods, there were 195, 273, 490, and 1252 such ar-
ticles. The growing fields of outcomes research and
health-technology assessment2 evaluate the efficacy,
cost effectiveness, and net benefit of new therapeutic
strategies to determine whether the associated increas-
es in expenditures for health care are justified. Quality-
of-life assessment measures changes in physical, func-
tional, mental, and social health in order to evaluate
the human and financial costs and benefits of new pro-
grams and interventions.
CONCEPTUALIZING QUALITY-OF-LIFE OUTCOMES
The terms “quality of life” and, more specifically,
“health-related quality of life” refer to the physical, psy-
chological, and social domains of health, seen as dis-
tinct areas that are influenced by a person’s experienc-
es, beliefs, expectations, and perceptions3-5 (which we
refer to here collectively as “perceptions of health”).
Each of these domains can be measured in two dimen-
sions: objective assessments of functioning or health
status (the y axis in Fig. 1), and more subjective percep-
tions of health (the x axis).6-8 Although the objective di-
mension is important in defining a patient’s degree of
health, the patient’s subjective perceptions and expec-
tations translate that objective assessment into the ac-
tual quality of life experienced (or Q, represented sche-
matically by the x and y coordinates in Fig. 1). Since
expectations regarding health and the ability to cope
From the Department of Biostatistics, Harvard School of Public Health
(M.A.T.); and the Department of Medicine, Joslin Diabetes Center, Brigham and
Women’s Hospital, and Harvard Medical School (D.C.S.) — all in Boston. Ad-
dress reprint requests to Dr. Testa at the Department of Biostatistics, Harvard
School of Public Health, 677 Huntington Ave., Boston, MA 02115.
Supported in part by a grant (R01 HS07767-03) from the Agency for Health
Care Policy and Research (to Dr. Testa).
1996, Massachusetts Medical Society.
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Copyright © 1996 Massachusetts Medical Society. All rights reserved.
835
with limitations and disability can greatly affect a per-
son’s perception of health and satisfaction with life, two
people with the same health status may have very dif-
ferent qualities of life.
Each domain of health has many components (for
example, symptoms, ability to function, and disability)
that need to be measured. Because of this multidimen-
sionality (Fig. 1), there is an almost infinite number of
states of health, all with differing qualities, and all quite
independent of longevity. For example, a person receiv-
ing mechanical ventilation who has no brain activity or
promise of recovery would not have even the most bas-
ic quality of life in each domain, even though potential-
ly living for a relatively long time. Between this extreme
and that of a fully healthy life, there is a continuum of
quality of life that can be measured.
MEASURING QUALITY OF LIFE
Translating the various domains and components of
health into a quantitative value that indicates the qual-
ity of life is a complex task, drawing from the fields of
clinimetrics,9 psychometrics, and clinical decision theo-
ry. Most researchers measure each quality-of-life do-
main separately, by asking specific questions pertaining
to its most important components. Simply asking one
question, such as “Please rate your quality of life or
overall health on a scale from 1 to 10,” although it may
provide a useful global assessment, leaves “quality of
life” and “overall health” ambiguously defined and the
quantity being measured too vague to be interpreted
more exactly. Relying solely on data indicating objec-
tive health status, such as physicians’ reports of symp-
toms, omits such relevant factors as a person’s thresh-
old for the tolerance of discomfort.10 Table 1 gives
examples of questions found on several scales common-
ly used to measure quality of life. Variation among
quality-of-life questionnaires is often related to the de-
gree to which they emphasize objective as compared
with subjective dimensions, the extent to which various
domains are covered, and the format of the questions,
rather than differences in the basic definition of quality
of life.
CONSTRUCTING SCALES OF MEASUREMENT
Because many of the components of quality of life
cannot be observed directly, they are typically evaluated
according to the classic principles of item-measurement
theory.16 This theory proposes that there is a true qual-
ity-of-life value, Q, that cannot be measured directly,
but that can be measured indirectly by asking a series
of questions known as “items,” each of which measures
the same true concept or construct. These questions are
then asked of the patient, and the answers are converted
to numerical scores that are then combined to yield
“scale scores,” which may also be combined to yield do-
main scores or other statistically computed summary
scores.17 If the items have been chosen properly, the re-
sulting scale of measurement, Z, should differ from the
836 THE NEW ENGLAND JOURNAL OF MEDICINE March 28, 1996

corresponding true value, Q, only by random error of measure. Z must measure Q, and not some other entity.
measurement and should possess several important When a scale purports to assess levels of anxiety, it
properties. should not be measuring levels of depression.
Coverage Responsiveness
The measurement of quality of life should address — Responsiveness is a measure of the association be-
that is, cover — each objective and subjective com- tween the change in the observed score, Z, and the
ponent (symptom, condition, or social role) that is im- change in the true value of the construct, Q. Since
portant to members of the patient population and quality of life is not directly observable, a change in
susceptible to being affected, positively or negatively, by Q also cannot be measured directly. Therefore, respon-
interventions. For example, the success of a new treat- siveness is often assessed by changing a criterion vari-
ment for Kaposi’s sarcoma in patients with the acquired able, C (for example, 0 may designate no treatment,
immunodeficiency syndrome (AIDS) can be measured and 1 treatment), when there is evidence to support a
in terms of reductions in the number and size of lesions, causal link between C and change in Q. The corre-
but the most relevant therapeutic benefit may actually sponding change on the scale Z is measured in respon-
be improvement in the patient’s ability to function on a siveness units (indicating the standard deviation of
daily basis, to work, to socialize, and to have a greater change under stable conditions — i.e., when no treat-
sense of well-being because of an improved self-image. ment is given) (Fig. 2). This method resembles an assay
of the relative potency of an active analgesic. Increas-
Reliability ing doses of the analgesic should result in decreasing
The process of measurement must yield values that pain. A valid pain scale needs to reflect these changes.
are consistent or remain similar under constant condi- Similarly, a quality-of-life scale should be constructed
tions, even in an extended series of repeated assess- to be responsive — that is, so that established objective
ments. As Figure 2 shows, the scale scores (Zs) should clinical treatments produce anticipated changes or dif-
have a low associated random error (E) of measure- ferences in the scale.
ment in repeated measurements, much as repeated lab-
oratory assays of the same serum sample should pro- Sensitivity
duce consistent results. Although a measure may be responsive to changes in
Q, gradations in the metric of Z may not be adequate
Validity to reflect these changes. Sensitivity refers to the ability
As Figure 2 shows, the observed scales should be val- of the measurement to reflect true changes or differenc-
id; that is, they target and measure what they claim to es in Q. Problems such as an inadequate range or de-
lineation of the response or the existence of ceiling and
floor effects in quality-of-life scales can mask important
Measurement Scales and therapeutically meaningful changes in quality of
Z life. In addition, meaningful changes for a single patient
Work are typically much smaller than differences between
Daily role
Personal relations patients, and therefore intervention studies require a
Positive affect greater sensitivity of measurement. For example, on the
Negative affect
Behavior SF-36, a commonly used, generic quality-of-life instru-
Symptoms ment, the Physical Functioning Scale (which ranges from
Social

Functioning
Disability 0 to 100, with higher values indicating better function-
Psychological

High
ing), has a mean of 94 for men 18 to 24 years of age and
Objective Health Status

High a mean of 80 for men 55 to 64 years of age.18 Therefore,

aging by 40 years is associated with a 14 percent decline
Physical

Quality of Life on the absolute scale. A young football player may rea-
Q(X,Y) sonably need a physical-functioning score of between 95
He Y
al
and 100 to play professional football. A decrease of 5 per-
th cent (5 of 100) may seem small on the absolute scale,
Do
m but it represents a 36 percent decrease (5 of 14) on the
ai relative 40-year aging scale and a 100 percent decrease
ns Low Low
(5 of 5) in the expected functional range of the young
Low High
Subjective Perceptions
athlete on the operative scale.
X EVALUATING QUALITY OF LIFE IN HEALTH
Figure 1. Conceptual Scheme of the Domains and Variables In- RESEARCH
volved in a Quality-of-Life Assessment. Three study designs are the most commonly used in
The x axis represents subjective perceptions of health, the quality-of-life evaluation. The first is the cross-section-
y axis objective health status, the coordinates Q(X,Y) the actual
quality of life, and Z the measurement of the actual quality of life al or nonrandomized longitudinal study, which describes
associated with a specific component (e.g., positive affect) or predictors of the quality of life (for example, specialty
domain (e.g., the psychological domain). vs. primary care). In these studies the samples must be
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Copyright © 1996 Massachusetts Medical Society. All rights reserved.
Vol. 334 No. 13 CURRENT CONCEPTS
relatively large (typically, with more than 500 patients
per comparison group, to allow for control for several
factors), and the measures must be applicable to broad
populations over a wide range of states of health. The
second common design is the randomized study of a
clinical intervention, which involves fewer subjects (typ-
ically, 500 patients or fewer per treatment group). In
these studies, the measures must reflect the nature of
the disease, be responsive to perceptually meaningful
changes, and be sensitive to changes within the range
of function specific to the disease. The third common
design is the study of cost effectiveness and cost–bene-
fit analysis, which estimates the incremental cost of a
program or treatment as compared with the program’s
incremental effects on health, which are usually meas-
ured by adjusting a clinical outcome such as survival by
the quality of life (for example, by measuring quality-
adjusted life years).19
ANALYTIC MODELS OF HEALTH — THE ROLE OF
QUALITY-OF-LIFE ASSESSMENT
The rationale for a quality-of-life assessment in clin-
ical research should be outlined in an analytic model
that describes or hypothesizes the relations among pre-
dictor variables and response variables and the time
frame during which the effects on quality of life are elic-
ited. Quality of life can be altered by both the immedi-
ate effects and the longer-term consequences of treat-
ment, especially in the case of chronic diseases. Figure
3, for example, shows how quality of life helps deter-
mine the overall net benefit of treatment for patients
with a chronic disease such as diabetes or hypertension.
Various treatments and regimens (such as insulin, oral
hypoglycemic agents, or antihypertensive agents) have
immediate effects (for example, within six months) on
the patient’s quality of life for various possible reasons:
an increase in side effects (such as hypoglycemia or fa-
tigue), a decrease in symptoms (such as frequent urina-
tion), or a change in lifestyle (such as insulin injection,
glucose self-testing, or diet). These effects can in turn
modify the patient’s compliance and affect the risk of
long-term complications of the disease. Finally, the de-
creased risk of long-term complications, such as ret-
inopathy, nephropathy, stroke, or cardiovascular dis-
ease, increases not only the absolute number of years of
life but also the amount of time during which the pa-
tient experiences better health and well-being.
SELECTING AN ASSESSMENT INSTRUMENT
The instruments and techniques used to assess qual-
ity of life vary according to the identity of the respond-
ent (that is, whether he or she is a clinician, patient,
relative, or care giver), the setting of the evaluation
and the type of questionnaire used (short form, self-
assessment instrument, interview, clinic-based survey,
telephone query, or mail-back survey), and the general
approach to the evaluation.
Generic instruments are used in general popula-
tions to assess a wide range of domains applicable to
a variety of health states, conditions, and diseases.11,20
They are usually not specific to any particular disease
The New England Journal of Medicine
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Copyright © 1996 Massachusetts Medical Society. All rights reserved.
837
Table 1. Representative Questions from Scales Used to Meas-
ure Various Domains of Quality of Life.
Physical domain
Functioning scale*
The following items are about activities you might do during a typical day.
Does your health now limit you in these activities? If so, how much?
a. Lifting or carrying groceries
b. Climbing one flight of stairs
c. Walking several blocks
d. Bathing or dressing yourself
Respond by choosing one of the following:
(1) Yes, limited a lot
(2) Yes, limited a little
(3) No, not limited at all
Symptom scale†
During the past month, have you experienced the following symptom
or feeling?
a. General weakness or fatigue
b. Confusion
c. Heartburn
d. Weight gain
e. Thirst
Respond either yes or no. If your answer is yes, answer the following
questions:
How often? (Once or twice, once or twice a week, often each week,
or almost daily)
How distressing has it been? (Not at all, somewhat, moderately, very
much, or extremely)
How much did this symptom keep you from enjoying life? Working effec-
tively? Feeling your best? (For each question, choose one of the fol-
lowing responses: Not at all, somewhat, moderately, very much,
or extremely.)
Psychological domain‡
Distress scale
a. How often during the past month have you felt so down in the dumps
that nothing could cheer you up? (depression)
b. How much of the time have you been a very nervous person? (anxiety)
c. During the past month, have you been in firm control of your behavior,
thoughts, emotions, and feelings? (emotional control)
Well-being scale
d. How happy, satisfied, or pleased have you been with your personal
life during the past month? (life satisfaction)
e. How much of the time, during the past month, did you feel relaxed and
free of tension? (general well-being)
f. During the past month, how much of the time have you generally
enjoyed the things you do? ( positive affect)
Responses for a, c, and f are given as examples:
For items a and f: Never, almost never, sometimes, fairly often, very often,
or always
For item c: No, and I am very disturbed; No, and I am somewhat disturbed;
No, not too well; Yes, I guess so; Yes, for the most part; or Yes, very
definitely
Work-performance domain§
If you are employed, during the past month have you:
a. Done as much work as others in similar jobs?
b. Worked for short periods or taken frequent rest because of your health?
c. Worked your regular number of hours?
Respond by choosing one of the following:
(1) All the time
(2) Most of the time
(3) Some of the time
(4) None of the time
*Four of 10 items on the Physical Functioning Scale (SF-36)11 are shown.
†Five of 51 items on the Side Effects and Symptoms Distress Checklist12-14 are shown.
‡Six of 38 items on the Mental Health Index3,5,12-14 are shown.
§Three of 6 items on the Work–Role Scale of the Functional Health Status Questionnaire15
are shown.
state or susceptible population of patients and are
therefore most useful in conducting general survey re-
search on health and making comparisons between
disease states.21,22
Disease-specific instruments focus on the domains
most relevant to the disease or condition under study
and on the characteristics of patients in whom the con-
838 THE NEW ENGLAND JOURNAL OF MEDICINE March 28, 1996

dition is most prevalent.23-25 A com-

prehensive bibliography has cross-
Safety
referenced instruments and disease Risk
26
states. Disease-specific instruments Reduction
are most appropriate for clinical tri- Efficacy
als in which specific therapeutic in-
terventions are being evaluated.27-29
Batteries of scales and modular in-
struments combine the generic and Compliance
the disease-specific approaches by Quality of Life
maintaining a core module of ques-
Years of
tions applicable to diverse disease Healthy Life
states and patient populations, to
which the questions most relevant to Convenience
the disease and therapy in question Net
12,30,31 Benefit
are added as needed. These in-
struments are especially useful in
large drug-development programs Treatment-related Patient-related Outcomes
and clinical trials conducted by co-
operative groups — for example, in
patients with cancer, human immu- Figure 3. The Role of Quality of Life in Determining the Net Benefit of Therapy for a
nodeficiency virus (HIV) disease, or Chronic Disease.
cardiovascular disease.13,14,32,33 This hypothetical model shows the relations among treatment-related influences
Index methods34-36 and instruments (safety, efficacy, and convenience), characteristics of patients (compliance), and meas-
urable outcomes (quality of life, risk reduction, years of healthy life, and net
that yield indexes22 combine various benefit).
domains and aspects of quality of life
to yield a single number. Such index-
es are calculated with utility estimation, regression tech- and policy planning.37 Since changes on quality-of-life
niques, or scoring algorithms. In this context, quality- scales often lack biologic meaning and involve unfa-
of-life assessment often involves assigning a number be- miliar measures, studies that relate these changes to
tween 0 and 1, called a “utility,” to a particular state of changes in more familiar or objective measures can be
health to represent a proportion of full health.19 easier to interpret.13 For example, Figure 4 shows how
changes on an overall quality-of-life summary scale can
INTERPRETING QUALITY-OF-LIFE EFFECTS be calibrated against changes in objectively stressful life
Studies of interventions must show that the observed events that are scored and summed in stress units. An
changes in patients that are due to treatments and pro- increase in stress of 27 units — approximately equiva-
grams of care are important and substantial enough lent to the stress associated with a minor violation of
to warrant further consideration in medical practice the law (11 units) plus a major change in sleeping habits
(16 units) spread over a six-week period — correspond-
ed to a six-week decrease in overall quality of life of
Quality-of-Life Measure, Z
Actual Quality of Life, Q

E approximately 0.1 responsiveness unit. Antihyperten-

sive therapy with either methyldopa or propranolol
Q(1) Z(1) produced a less favorable mean change in positive well-
E being than therapy with captopril (0.8 and 0.5 respon-
Q
siveness unit, respectively).32 In patients with relatively
Z
E advanced HIV disease, the mean overall decrement in
quality of life was approximately 0.6 responsiveness
Q(0) Z(0)
unit when an AIDS-defining illness subsequently devel-
C E oped (unpublished data). Patients who underwent hip
C(0) C(1) arthroplasty had a mean improvement of between 0.64
Criterion Variable, C and 0.94 SD unit, depending on the quality-of-life scale
E
used.38
E Reliability Responsiveness
Validity
Z
Sensitivity How does one interpret whether changes on the
multiple quality-of-life subscales are meaningful and
Figure 2. Properties Essential to a Measure of Quality of Life — whether they are predominantly positive or negative?
Reliability, Validity, Responsiveness, and Sensitivity. First, the clinician should not make the mistake of trans-
Q denotes the actual quality of life, Z the quality of life as meas- lating mean treatment-related differences (shifts in qual-
ured with a questionnaire, and C the presence or absence of an ity of life for an entire population) directly to an indi-
intervention (e.g., 0  no treatment, 1  treatment) that is known to vidual patient. For example, we might assume that the
alter Q and used to establish criteria for the evaluation of respon-
siveness. The equilateral triangles represent the change in the
decrease in quality of life required for a change in clin-
measures. The four criteria are described in the text ical management for an individual patient is 0.6 respon-
in greater detail. siveness
The New England Journal unit, or a worsening of 5 to 20 percent on the
of Medicine
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Copyright © 1996 Massachusetts Medical Society. All rights reserved.
Vol. 334 No. 13 CURRENT CONCEPTS 839

0 es, such as the following: What is the effect of disease-

Score for Negative Life Events
Major change in sleeping habits (16)
20 Major change in working conditions (20)
Death of a close friend (37)
40
Major personal
illness (53)
60
Divorce (73)
80
Death of a spouse (100)
100
0.3 0.2
Change in Quality of Life (SD Units)
Figure 4. Calibration of Changes in Overall Scores for Quality of
Life with the Corresponding Scores for Stressful Life Events.
A total of 2938 pairs of change scores were obtained for 824
male patients with hypertension who participated in two ran-
domized clinical trials of antihypertensive therapy13 (and unpub-
lished data). The changes in quality of life shown are computed
from statistical summary scores of 11 components from the
social, psychological, and physical domains.13 Examples of life
events (followed in parentheses by their associated scores) are
shown in the body of the figure, with lower negative numbers in-
dicating greater stress and worse quality of life. The thick line is
the regression slope, and the upper and lower dashed lines the
standard error.
absolute scale, depending on the sensitivity of the
39
scale. Then a mean decrease in the population of only
0.3 unit due to the use of a less effective therapy could
result in a worsening by 0.6 unit or more for approxi-
mately 11 percent of patients and could therefore re-
quire a change in disease management for those pa-
37
tients. Even a seemingly small mean decrease of 0.15
unit (1 to 6 percent on the absolute scale) should neces-
sitate a change of treatment for 5 percent of patients.
In addition, testing overall differences with a global hy-
pothesis,40,41 using summary scales,17 and other analytic
42
considerations can help in interpreting the overall di-
rection and importance of quality-of-life effects.
THE NEED FOR PRACTICAL CLINICAL APPLICATIONS
The effects of medical treatments and programs on
quality of life should not be ignored simply because such
43
effects are difficult to measure. Furthermore, the esti-
mated advantage of one treatment over another in cost
effectiveness can be substantially altered, and even re-
versed, by adjusting the primary measure of effective-
ness for quality of life. However, the degree to which
practical knowledge is gained from quality-of-life re-
search depends on whether the rationale for the assess-
ment has practical implications and on whether quality-
of-life changes and treatment effects can be understood
and interpreted by clinicians and health policy planners.
A recent editorial44 criticized the routine inclusion of
quality-of-life evaluation in clinical trials even when the
structure of the evaluation and its rationale appear ill-
defined. Although quality-of-life research has its roots
in the social sciences, it will be fully accepted by health
care practitioners only when it answers questions di-
rectly related to clinical programs and therapeutic
The Newchoic-
England Journal of Medicine 1980:184-227.
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Copyright © 1996 Massachusetts Medical Society. All rights reserved.
Minor violation of the law (11) management programs, not only on long-term com-
plications but also on the day-to-day quality of life and
Trouble with boss
(23)
compliance of patients with chronic diseases, such as
Sexual difficulties (39) diabetes, hypertension, and arthritis? Are relatively small
Being fired from work (47)
gains in survival among patients with a limited life ex-
pectancy, such as those with advanced AIDS or cancer,
offset by reductions in the patients’ quality of life dur-
Death of a close family member (63)
ing toxic and aggressive long-term therapy or chemo-
therapy? Do cost-containment programs in managed
health care actually increase costs to employers because
of decreased functioning and productivity of employees?
0.1 0.0 To answer these and similar questions, we should use fu-
ture research to demonstrate the links among medical
interventions, clinical and physiologic changes, and qual-
ity of life so that the practicing clinician can better
understand the clinical implications of these measures,
and so that health care planners can use them in setting
priorities.
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